Generalized Anxiety Disorder and Social Anxiety Disorder:

广泛性焦虑症和社交焦虑症：

• 批准号: 8939981
• 负责人: james r blair
• 金额: $ 13.63万
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8939981
• 关键词: Adult; Affective; Alcohol abuse; Amygdaloid structure; Anger; Anxiety; Anxiety Disorders; Commit; Data; Decision Making; Development; Disease; Drug abuse; Emotional; Fright; Functional Magnetic Resonance Imaging; Functional disorder; General Population; Generalized Anxiety Disorder; Goals; Impairment; Individual; Intervention; Learning; Life; Mental Depression; Nature; Neurobiology; Participant; Patients; Persons; Prevalence; Process; Protocols documentation; Psychological reinforcement; Punishment; Relative (related person); Rewards; Role; Social Phobia; Stimulus; Stress; Suggestion; Suicide; Uncertainty; Work; base; cognitive neuroscience; design; economic cost; functional disability; high risk; neuromechanism; relating to nervous system; response; social; therapeutic target

There were developments in two strands of our work with patients with GSP and GAD over the past 12 months: The first concerns the specific nature of the functional impairment seen in GSP. In previous work, we have shown that GSP does not simply represent a heightened amygdala response to social threats (angry expressions). Instead, there appears additionally to be atypical self-referential processing of social information. Following this work, we considered that it might be possible to reduce patients' heightened amygdala response to social threats by altering their self-referential processing. Specifically, we investigated whether the presentation of simple statements that either praised the self, criticized the self or were neutral had an impact on the amygdala response to social threats. Notably, patients with GSP showed exaggerated amygdala responses to social threats (angry expressions) relative to comparison individuals that were particularly increased if they followed a self-critical statement. In contrast, group differences in amygdala response to angry expressions were significantly reduced following self-praising statements. These data indicate the important modulatory role of self-referential processing over the anxiety responses of patients with GSP and stress the importance of developing treatments focused on positive self referential processing. The second concerns the specific nature of the functional impairment seen in GAD. In particular, we have been examining whether some of the problems in emotional responding in GAD that we observed in our preliminary work with patients with this disorder might manifest in difficulties on decision-making tasks. In previous work, we had demonstrated that patients with GAD, relative to patients with GSP and healthy adults, show impairment on very simple reinforcement-based decision-making tasks. Such a task is the passive avoidance task. On this task, the participant must learn to respond to some stimuli as doing so engenders reward (monetary gain). However, they must also passively avoid others (do nothing) as responding to these bad stimuli will engender punishment (monetary loss). Participants with GAD respond less to the good stimuli and more to the bad stimuli than patients with GSP and healthy adults. Our goal this year was to determine the computational basis of this impairment at the neural level. In other work, we have investigated the neural representation of prediction errors (the difference between the reward expected by the person and that received) and expected value (the expected reward from committing the action). The accurate representation of prediction errors is critical for learning; the greater the error, the greater the learning that should occur. The accurate representation of expected value is critical for successful decision-making; it is important to select the response associated with the greatest reward. Using a modified version of the passive avoidance task specifically designed for fMRI, we determined that patients with GAD show significant impairment in the representation of prediction error within caudate relative to patients with GSP and healthy participants. It is possible that uncertainty in decision choice, consequent on this impairment, contributes to the worry shown by patients with this disorder.

在过去的12个月里，我们对GSP和GAD患者的工作有两个方面的进展： 第一个问题涉及普惠制中所见的功能损害的具体性质。在以前的工作中，我们已经表明，GSP不仅仅代表杏仁核对社会威胁(愤怒表情)的高度反应。相反，似乎还有一种非典型的社会信息自我参照加工。在这项工作之后，我们认为有可能通过改变患者的自我参照过程来降低患者对社会威胁的高度杏仁核反应。具体地说，我们调查了表扬自我、批评自我或中立的简单陈述是否会对杏仁核对社会威胁的反应产生影响。值得注意的是，与对照组相比，患有GSP的患者表现出对社会威胁(愤怒表情)的夸大反应，如果他们遵循自我批评的声明，这种反应尤其明显。相比之下，在自我表扬后，杏仁核对愤怒表情的反应差异显著减少。这些数据表明，自我参照加工对GSP患者的焦虑反应具有重要的调节作用，并强调了开发以积极自我参照加工为重点的治疗方法的重要性。 第二个问题涉及GAD中所见的功能障碍的具体性质。特别是，我们一直在研究我们在对患有这种疾病的患者的初步工作中观察到的GAD在情绪反应方面的一些问题是否可能表现为决策任务中的困难。在之前的工作中，我们已经证明，与GSP患者和健康成年人相比，GAD患者在非常简单的基于强化的决策任务中表现出障碍。这种任务就是被动回避任务。在这项任务中，参与者必须学会对某些刺激做出反应，因为这样做会产生回报(金钱收益)。然而，他们也必须被动地避免其他人(什么都不做)，因为对这些坏刺激的反应会产生惩罚(金钱损失)。与GSP患者和健康成人相比，GAD患者对好刺激的反应更少，对坏刺激的反应更多。我们今年的目标是在神经水平上确定这种损伤的计算基础。在其他工作中，我们研究了预测误差(个人期望的回报与收到的回报之间的差异)和期望值(做出行动的预期回报)的神经表征。预测误差的准确表示对学习至关重要；误差越大，应该进行的学习就越多。期望值的准确表示对于成功的决策至关重要；选择与最大回报相关的反应是很重要的。使用专门为fMRI设计的被动回避任务的修改版本，我们发现GAD患者相对于GSP患者和健康参与者在尾状体内预测错误的表征方面存在显著障碍。这可能是由于这种损害导致的决策选择的不确定性导致了这种疾病患者表现出的担忧。